Proposed here is a study of the role of total PCBs, individual PCB congeners, DDT and mirex in the etiology of postmenopausal breast cancer. Serum levels of these environmental contaminants will be evaluated. In addition, the association with risk of genetic polymorphisms of enzymes involved in carcinogen metabolism and detoxification (the cytochrome P450 enzymes CYP2D6 and CYP1A1, and glutathione-S-transferase) will be examined. Finally, effect modification of the association of the environmental contaminants with risk by the genetic polymorphisms will be assessed. This study will use stored, frozen (-70 degrees C) blood specimens collected as part of a larger case-control study of diet, reproductive and other factors in risk of postmenopausal breast cancer. Cases (n= 150) have primary, histologically confirmed disease. Population controls (n= 150) will be matched to cases on age and date of blood draw and frequency matched to cases on other breast cancer risk factors other than family history of breast cancer. New blood samples will be drawn for the DNA determinations. Interview data have already been collected on predisease usual diet, medical history, reproductive history and family history of cancer. This study provides an important opportunity for efficient examination of potentially important environmental contaminants in conjunction with evaluation of genetic susceptibility and other known risk factors, in the northeastern U.S., a geographic region at high risk of breast cancer.